RDX-002(Response Pharmaceuticals)

FALLS CHURCH, VA, USA I October 17, 2024 I Response Pharmaceuticals, Inc., a clinical-stage company focused on weight management and metabolic health in high-risk populations, today announced the initiation of enrollment in a Phase 2 trial evaluating the company’s drug candidate, RDX-002, for post-GLP-1 weight rebound. The study is assessing the effect of RDX-002, an investigational first-in-class inhibitor of intestinal microsomal triglyceride transfer protein (iMTP), on post-prandial triglyceride levels as well as associated effects on weight and other cardiometabolic risk factors in individuals discontinuing the GLP-1 agonists, semaglutide or tirzepatide, for the treatment of obesity. “There is a significant and growing unmet need in patients coming off GLP-1 agonists who rapidly regain much of the weight lost while on these drugs, which reverses the cardiometabolic benefits associated with their weight loss” said Eric Keller, Response Pharmaceuticals’ Founder and CEO. “In our initial studies in antipsychotic-induced weight gain (“AIWG”), RDX-002 has shown promise in counteracting weight gain associated with the use of common anti-psychotics with good initial tolerability. We are excited to evaluate its effect in this second and important weight management setting while we continue development for AIWG.” “An emerging issue in the treatment of obesity is the regain of body weight and associated cardiometabolic risk factors that occurs when patients stop GLP-1 agonist treatment,” Professor Chris Packard, Institute of Cardiovascular and Medical Sciences, University of Glasgow stated. “A treatment such as RDX-002, may help to minimize this weight rebound and provide patients a ‘soft landing’ following GLP-1 agonist discontinuation.” “Obesity is a chronic, complex disease associated with increased risk for significant cardiovascular and metabolic comorbidities including hyperlipidemia, insulin resistance, type 2 diabetes, hypertension, and cardiovascular disease,” Dr. Bill Sasiela, Chief Medical Officer noted. “While GLP-1 agonists such as semaglutide and tirzepatide have shown the ability to significantly reduce weight and the associated CV/metabolic risk factors in obesity, the vast majority of patients eventually discontinue these drugs. RDX-002 has shown promise in counteracting drug-induced weight gain by decreasing the absorption of dietary fats from the intestine, thereby reducing caloric intake. This results in improved levels of post-meal triglycerides, “bad” LDL-cholesterol, and glycemic control, all of which are established risk factors for developing cardiovascular disease and diabetes.” The trial ( NCT06640972 ) is a double-blind study evaluating the efficacy and tolerability of RDX-002 over 12 weeks in patients who have lost significant weight using GLP-1 agonist drugs but are planning to discontinue the treatment. Data from this study are expected in the second half of 2025. Response is also pleased to announce that we will be presenting the results from our proof-of-concept study of RDX-002 in antipsychotic induced weight gain at Obesity Week 2024 in San Antonio on November 4 th . See https://obesityweek.org for program and full details. About RDX-002 RDX-002, Response Pharmaceuticals’ lead candidate, is an investigational first-in-class, potent, selective, and gut-specific small molecule inhibitor of intestinal microsomal triglyceride transfer protein (iMTP). The overall effect of iMTP inhibition is a decrease in the amount of triglycerides and cholesterol – and therefore calories – delivered to the body after a meal. RDX-002 is being developed as a therapy to combat drug-induced weight gain and improve cardiometabolic risk, including in patients taking life-saving anti-psychotic medications and those discontinuing GLP-1 agonists for the treatment of obesity. RDX-002 has been studied in multiple Phase 1 and Phase 2 clinical trials including 496 healthy subjects and patients dosed for up to 84 days. In these studies, RDX-002 lowered post-prandial triglyceride levels, circulating levels of low-density lipoprotein cholesterol (LDL-C), and reduced weight. RDX-002 was generally well-tolerated, with adverse events restricted to mostly mild to moderate GI effects. No serious adverse events have been attributed to RDX-002. RDX-002 is being developed under an exclusive world-wide license from Sanofi S.A. About Response Pharmaceuticals Response Pharmaceuticals is a clinical-stage biopharmaceutical company focused on developing treatments for weight management and metabolic health in high-need patient populations. The company is building its portfolio with an initial focus on helping those taking antipsychotic medications for disabling mental illnesses to combat weight gain and metabolic dysregulation associated with these treatments and accompanying elevated morbidity and mortality risk. Use in patients coming off weight loss drugs as well as potential other settings in which clinically significant weight gain and/or adverse metabolic changes are prevalent is also being explored. For more information, please visit https://www.responsepharmaceuticals.com . SOURCE: Response Pharmaceuticals

The Virginia-based company has revealed promising results from its phase 1b clinical trial assessing RDX-002, a novel small molecule therapy designed to address this pressing medical concern. The trial, conducted over two weeks, has yielded findings that emphasize the potential of RDX-002 in mitigating the adverse metabolic effects associated with antipsychotic medications, the company says. Antipsychotic-induced weight gain is a well-documented phenomenon that poses a significant challenge in the management of mental illnesses such as schizophrenia, depression, and bipolar disorder. These conditions often necessitate the use of antipsychotic medications to alleviate symptoms and improve patients' quality of life. However, a common side effect of many antipsychotics is rapid and clinically meaningful weight gain, which can occur within the first few weeks of treatment and persist over the long term. This weight gain, Response says, not only leads to poor adherence to medication regimens but also contributes to the development of metabolic abnormalities such as hyperlipidemia and hyperglycemia, thereby increasing the risk of cardiovascular disease and diabetes. Dr. Joseph Coyle, emeritus chair of psychiatry and neuroscience at Harvard Medical School, highlighted the significance of addressing AIWG. Rapid weight gain and obesity He said “Antipsychotic medications are essential treatments that help millions of patients live better lives but can be associated with rapid weight gain and obesity. This often leads to poor adherence to treatment and reduced quality of life and contributes to long-term cardiometabolic morbidities including decreased life expectancy.” googletag.cmd.push(function () { googletag.display('text-ad1'); }); In light of these challenges, Response Pharmaceuticals embarked on a clinical trial to evaluate the safety and efficacy of RDX-002, a first-in-class candidate treatment aimed at preventing the rapid weight gain associated with antipsychotic medications. The phase 1b trial enrolled 24 healthy, antipsychotic-naïve volunteers who were initially treated with olanzapine, a widely used antipsychotic known for its propensity to induce weight gain. During the trial, people were randomized to receive either RDX-002 in addition to olanzapine or olanzapine alone for the duration of the second week. The primary endpoint of the trial was to assess the impact of RDX-002 on postprandial triglycerides (ppTGs), a key marker of metabolic health. The results, Response says, were striking, with subjects in the RDX-002 cohort demonstrating a remarkable 82% reduction in postprandial triglycerides compared to those receiving olanzapine alone. Dr. Paul Sweetnam, chief science officer of Response Pharmaceuticals and lead inventor of RDX-002, elaborated on the implications of these findings, he said: “Treatment with the iMTP-inhibitor RDX-002 significantly reduced ppTGs and blunted the weight gain in OLAN-treated subjects indicating a potential role in the treatment and prevention of AIWG.” Reduction in weight gain In addition to the favorable effects on postprandial triglycerides, the company said exploratory analyses revealed a notable reduction in weight gain among patients treated with RDX-002. While patients receiving olanzapine alone experienced a significant increase in body weight during the first and second weeks of treatment, those receiving RDX-002 demonstrated minimal weight change, highlighting the potential of RDX-002 to mitigate the metabolic effects of antipsychotic medications. Response Pharmaceuticals CEO Eric Keller is optimistic about the impact of RDX-002. He said: “This is very promising news for patients who have long fought to manage not only severe mental illness but also the syndrome of AIWG and its associated morbidities.” The positive results from the phase 1b trial have paved the way for further clinical development of RDX-002. Response Pharmaceuticals is now preparing to initiate a phase 2 clinical trial to evaluate the efficacy of RDX-002 in patients with bipolar depression and schizophrenia initiating olanzapine therapy. The trial, the company says, will be a placebo-controlled 12-week study designed to assess changes in weight gain and postprandial triglycerides, to further validate the potential of RDX-002 as a treatment for AIWG. Antipsychotic-induced weight gain remains a significant unmet medical need, affecting millions of individuals worldwide. Response Pharmaceuticals' forward-thinking approach with RDX-002 aims to offer hope for improved outcomes and enhanced quality of life for patients grappling with this challenging side effect of antipsychotic medications. As the company continues to advance its clinical development program, there is optimism that RDX-002 may emerge as a much-needed therapeutic option for individuals at risk of AIWG.